Genetics of Migraine: Implications for novel treatments

Abstract

Migraine is a severe neurological disorder that affects a significant proportion of the population. Prevalence estimates for the disorder vary between 12 and 25% depending on the population studied. The disorder has a significant genetic component showing high levels of familial aggregation. Although a number of genes involved in a rare and severe sub-type of migraine, termed familial hemiplegic migraine have been identified, the number and identity of all the genes involved in the more common types of migraine have yet to be defined. Genetic characterisation of migraine have implicated genomic regions on a number of chromosomes, including 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. In addition, candidate gene association studies have identified several susceptibility variants that are implicated in the disorder. Neurotransmitter pathways have been the main focus of studies investigating the molecular mechanisms of the disorder. However vascular and hormonal triggers disturbances also occur in migraineurs, as highlighted by alterations in cerebral blood flow and hormonal triggers of migraine, particularly in women and hence factors affecting these functions may also be involved. This presentation will focus on migraine gene studies in our laboratory, including recent studies implicating dopamine beta hydroxylase and MTHFR functional variants, as well as presenting an overview of results from a recently completed clinical trial that involved genetic profiling in conjunction with a nutriceutical therapeutic treatment. These clinical trial results are very promising and highlight the potential importance of pharmacogenetic interventions in this disorder.